Cerebellar Functional Alterations During Executive Functioning Are Associated With General Psychopathology in a Cross-Diagnostic Sample

Abstract

Background

Accumulating evidence points to the cerebellum’s role in executive functioning (EF) and transdiagnostic psychopathology. A general psychopathology p-factor, capturing shared variation across mental disorders, has been associated with EF deficits and structural alterations within the posterior cerebellum. One hypothesis is that the cerebellum contributes to general psychopathology because of its role in executive dysfunctions.

Methods

To test this hypothesis, we used functional magnetic resonance imaging (fMRI) data from the University of California, Los Angeles Consortium for Neuropsychiatric Phenomics study including 257 adults (ages 21–50 years) who met diagnostic criteria for schizophrenia, bipolar disorder, or attention-deficit/hyperactivity disorder or were healthy control participants. We examined relationships between p-factor scores and cerebellar activation across participants during 3 fMRI tasks of working memory (spatial capacity), cognitive flexibility (task switching), and response inhibition (stop signal). Specificity analyses of cerebellar activation associated with internalizing, externalizing, and thought disorder factor scores were also conducted.

Results

Robust posterior cerebellar activation was identified during all 3 fMRI tasks. Higher p-factor scores were associated with poorer EF performance, greater activation of cerebellar crus I/II and lobule VIIIA/B with increasing working memory difficulty, and greater activation of lobules VI and VIIIA/B during successful inhibition (R² range = 0.078–0.108). Associations between cerebellar activation and internalizing, externalizing, and thought disorder factor scores were largely overlapping with associations with the p-factor.

Conclusions

These novel results identify functional alterations within the posterior cerebellum during EF in individuals high in general psychopathology. Greater activation of the posterior cerebellum may be a transdiagnostic dysfunction reflecting inefficient information processing during EF present across disorder categories.